A 1β-methylcarbapenem compound exhibits an excellent antibacterial action against a wide range of pathogenic bacteria and also has a high stability in a living body; therefore, the compound is one of the most-watched antibacterial agents. As an intermediate useful for synthesizing the above-mentioned 1β-methylcarbapenem compound, an azetidinone compound represented by general formula (1):
has been known (see, Patent documents 1, 2 and 3). The compound represented by the formula (1) (hereinafter, sometimes abbreviated as Compound (1)) is a very important and useful intermediate, since the compound generally allows the synthesis of 1β-methylcarbapenem compounds through only two steps of coupling Compound (1) to a thiol compound and deprotecting the resulting intermediate, as described in Patent document 4.
As the method for crystallization of Compound (1), a crystallization method in which n-hexane is added dropwise to a methylene chloride solution containing Compound (1) is disclosed in Patent document 1. Further, a crystallization method in which water is added to a solution of Compound (1) obtained by a synthetic reaction, containing an organic solvent such as ethyl acetate or methylisobutylketone, thereby preparing a mixed solvent and then a poor solvent is added to the mixed solvent is disclosed in Patent document 2. Furthermore, a crystallization method in which a solution of Compound (1) obtained by a synthetic reaction, containing an organic solvent such as ethyl acetate or methylisobutylketone, is washed with water in the presence of methylethylketone, and a water-soluble component is removed by a liquid separation procedure followed by a post-treatment procedure such as condensation, and then, a poor solvent is added to the resulting solution is disclosed in Patent document 3. However, when the present inventors replicated these methods, it was found that the methods have problems such as:    (A) a compound represented by general formula (2):
a compound represented by general formula (3):
and/or a compound represented by general formula (4):
is contained in the obtained crystal as an impurity in an amount of 0.4% or more; and such a crystal is not sufficiently satisfied in terms of the quality; and it is necessary to control the amount of the impurity to be further reduced, considering the crystal is used as a useful intermediate from which a bulk drug can be synthesized in short steps;    (B) a filtration time is prolonged in the case of industrial scale production because of the poor filterability of the crystal, leading to a decrease in productivity, when the crystallized slurry is subjected to a solid-liquid separation to obtain the crystal; and further, Compound (1) is likely to be decomposed and is unstable in a state of a solution; therefore, the quality is deteriorated due to the increase of the impurity, when the filtration time is prolonged.Furthermore, it was found that the methods have problems from a practical point of view, such as:    (C) when the present inventors studied the storage stability at 60° C. of Compound (1) in a crystalline form obtained by the same method as described in Patent document 4, 20% decomposition was observed in 8 days, and the stability of Compound (1) under a severe condition such as at 60° C. is low; and therefore, Compound (1) in a crystalline form is not always suitable for a long-term storage in the consideration of industrial scale distribution and storage, although it is disclosed in Patent document 4 that Compound (1) in a crystalline form is not decomposed even if Compound (1) is stored at 40° C. for 20 days and the stability of Compound (1) is extremely high.
Patent document 1: JP 3479720 B
Patent document 2: JP 8-311092 A
Patent document 3: JP 2000-44587 A
Patent document 4: JP 3080417 B